tbuckley/cabot-search huggingface dataset:
Unmasking ethnic disparities in Asian representation in U.S. oncology training programs.
Authors: Patricia Mae Garcia Santos, Fumiko Chino, Mylin Ann Torres, Gita Suneja, Curtiland Deville, Neha Vapiwala
Journal: Journal of Clinical Oncology (2023)

e18548 Background: Asian Americans are not traditionally considered underrepresented in oncology; however, prior analyses of oncology workforce representation have not disaggregated Asian race by ethnicity. This study assessed Asian representation in U.S. oncology training programs by country of origin. Methods: All trainees with self-reported race/ethnicity data in U.S. Radiation (Rad Onc), Medical (Med Onc), Pediatric (Peds Onc), and Surgical Oncology (Surg Onc) programs were identified using 2013-2022 data from the Association of American Medical Colleges. Complex Surgical, Gynecologic, and Orthopedic Oncology programs were included within the Surg Onc category. Asian race was disaggregated by available subgroups (i.e., Bangladeshi, Cambodian, Chinese, Filipino, Indian, Indonesian, Japanese, Korean, Pakistani, Taiwanese, and Vietnamese). Asians with &gt; 1 or no subgroup classification were excluded. Representation quotients (RQ) were used to measure representation relative to the U.S. census population adjusted by age and year, whereby RQ = 1 denoted proportional representation; RQ &gt; 1 and RQ &lt; 1 denoted representation greater or less than expected; RQ = 0 denoted no representation. Linear regression assessed trends in RQ over time for each subgroup. Results: Overall, 27% of oncology trainees identified as Asian (31% Rad Onc, 30% Med Onc, 30% Peds Onc, 19% Peds Onc, 16% Surg Onc). Apart from Indonesians in Rad Onc (median [IQR] RQ, 1.21 [0-3.54]), RQ = 0 for all Indonesians, Cambodians, and Laotians, while median RQ was &lt; 1 for all Filipinos, regardless of program type. In contrast, all other Asian ethnic subgroups had median RQ values &gt; 1, except for Taiwanese and Vietnamese fellows in Surg Onc (0.84 [0.45-0.96]) and Peds Onc (0.43 [0.30-0.63]), respectively. Among Filipinos, median RQ values for Med Onc (0.39 [0.31-0.48]) and Peds Onc (0.51 [0.45-0.58]) were approximately half that of their respective primary residencies (Internal Medicine, 0.75 [0.75-0.73]; Pediatrics: 0.97 [0.99-91]). From 2013-2021, representation remained largely stable for all ethnic groups, with the exception of increased representation among Taiwanese Med Onc (RQ slope [95%CI], 2.96 [1.81, 4.11]; p&lt; 0.001) and Indonesian Rad Onc (0.94 [0.53 to 1.35]; p= 0.001) trainees; and decreased representation among Indian Med Onc (-0.44 [-0.65, -0.23]; p= 0.002) and Korean Surg Onc (-0.04 [-0.61, -0.20], p= 0.003) trainees. No changes in Filipino representation were observed. Conclusions: In this first workforce analysis of oncology trainees to disaggregate Asian race by ethnicity, Cambodians, Filipinos, Indonesians, and Laotians were consistently underrepresented in oncology training programs. Further investigation is needed to understand these differences to ensure that efforts to promote diversity in oncology avoid overlooking ongoing imbalances in representation and inclusion in the U.S. physician workforce.
NMR metabolomics in bladder cancer: Identification and monitoring of serum biomarkers during Pt-based treatment.
Authors: Roberta Giorgione, Elisabetta Gambale, Virginia Rossi, Marinella Micol Mela, Laura Doni, Giandomenico Roviello, Roberta Renda, Giulia Venturi, Adriano Pasqui, Andrea Zenoni, Andrea Bernini, Serena Pillozzi, Lorenzo Antonuzzo
Journal: Journal of Clinical Oncology (2023)

3057 Background: To date, predictive and prognostic biomarkers for Bladder Cancer (BC) are lacking. Metabolomics, the study of small molecules involved in metabolism, aims to identify diagnostic, predictive and prognostic biomarkers. Overall, BC shows perturbations of various metabolic pathways, involved in biochemical reactions essential for energy production and for the maintenance of the REDOX balance, as well as in the metabolism of purines and pyrimidines. The main objective of this study is to characterize the serum metabolic profile of patients with BC undergoing platinum-based chemotherapy (Pt-CT), to identify the alterations induced by CT and evaluate the associated deregulated metabolic pathways, in order to identify potential biomarkers, prognostic and predictive of response to treatment. Methods: We enrolled patients with BC undergoing Pt-CT in different settings (neoadjuvant, adjuvant or metastatic). For each patient, a blood sample was collected before the start of each CT cycle (T0, T1, Tn). Metabolomic analysis was performed using the Bruker Avance 600 spectrometer. At baseline (T0), the metabolomic profiles of BC patients were compared with that of age- and sex-matched healthy controls. Major metabolites up- or down-regulated in patients with BC at baseline, were then monitored during CT (T1, Tn). Results: 14 patients were enrolled. When compared with age- and sex-matched healthy controls, patients with BC had elevated levels of acetate and acetone (ketone bodies), hypoxanthine, trimethylamine N-oxide (TMAO), glutamate, lactate, phenylalanine, and ornithine, and decreased levels of carnitine, choline, betaine, aspartate, threonine, 2-hydroxybutyrate, 2-aminobutyrate and histidine. When monitored during CT, hypoxanthine, glutamate, and aspartate levels increased; acetone, acetate and TMAO instead had a decreasing trend. Conclusions: The results of our pilot study confirm perturbations in several metabolic pathways: up-regulation of lactate, ketone bodies, hypoxanthine, phenylalanine, and glutamate levels in BC patients reflects altered glycolysis, fatty acid, purine, and amino acid metabolism, respectively. In addition, TMAO may play a role in the development of BC by promoting a pro-inflammatory and oxidative stress state. Furthermore, monitoring these metabolites could be a useful tool for predicting response to treatments. To our knowledge, there are no metabolomic studies that evaluated BC patients receiving CT and that included longitudinal monitoring to identify any changes in the metabolic profile induced by treatment.
Reliability of audiovisual information on lung cancer from cancer organizations.
Authors: Hardik Dand, Celinne Macarulay, Preetham Reddy, Michael Papakonstantinou
Journal: Journal of Clinical Oncology (2023)

11020 Background: In the US, lung cancer is the leading cause of cancer death and second most common cancer. YouTube (YT), a social media platform with billions of users, can improve knowledge but also disseminate inaccurate information. Research has shown YT plays a key role in public health. This study assesses the reliability of YT videos about lung cancer using its own algorithm compared to videos from three cancer organizations. Methods: We searched “lung cancer” on YT and selected 8 videos with the most views. Then, “lung” was searched from YT profiles of American Cancer Society (ACS), National Cancer Institute (NCI), and National Comprehensive Cancer Network (NCCN). Criteria required videos to be less than 10 minutes and have “lung” in the description. Videos were excluded if not in English, older than 15 years, patient stories, or sponsored by pharmaceutical entities. The videos were graded by 3 independent medicine residents using the validated methods of Patient Education Materials Assessment Tool Understandability and Actionability (PU and PA) and Journal of the American Medical Association (JAMA) scoring. Higher percentages of PU and PA represented more understandable and actionable material. Higher JAMA score (up to 4) indicated better quality of information. Descriptive statistics and non-parametric Kruskal-Wallis tests were done. Results: A total of 36 videos were identified. PU mean was 74.2% (SD 21.4) in YT compared to 62.4% (SD 15.2), 53.1% (SD 28), and 58.8% (SD 13.9) for ACS, NCI, and NCCN respectively. PA mean was 46.6% (SD 46.8) for YT compared to 12.9% (SD 31.7), 38.9% (SD 53.6), and 8.2% (SD 21.2) for ACS, NCI, and NCCN respectively. A statistically significant higher median actionability score can be seen in YT. The JAMA average was 1.9 (SD 0.2) for YT compared to 2.1 (SD 0.1), 2.3 (SD 0.6), and 2.0 (SD 0) for ACS, NCI, and NCCN respectively. While a statistically significantly higher median JAMA score is seen in NCI videos, no meaningful difference can be extrapolated given all average scores of roughly 2. Conclusions: YT produced videos of higher understandability and actionability compared to videos from cancer organizations. As patients continue to rely on social media for information, trusted cancer sources should develop more reliable material for improved patient education. Comparison of scores from averages of 3 reviewers. [Table: see text]
HER2 testing in the MOUNTAINEER trial: Analysis of treatment response based on central HER2 assessment using IHC/ISH and NGS.
Authors: John H Strickler, Andrea Cercek, Kimmie Ng, Salvatore Siena, Thierry Andre, Eric Van Cutsem, Christina Wu, Andrew Scott Paulson, Joleen M. Hubbard, Andrew L. Coveler, Christos Fountzilas, Adel Kardosh, Pashtoon Murtaza Kasi, Heinz-Josef Lenz, Kristen Keon Ciombor, Elena Elez, Michael Stecher, Pauline Cronin, Mark Bieda, Tanios S. Bekaii-Saab
Journal: Journal of Clinical Oncology (2023)

3528 Background: Tucatinib (TUC) is a highly selective HER2-directed TKI approved by the FDA in combination w/trastuzumab (Tras) for treatment (tx) of pts w/ RAS wild-type HER2+ unresectable or metastatic colorectal cancer (mCRC) that has progressed following tx w/ fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy. There are currently no established best practices for HER2 testing/interpretation in mCRC. Here we present results of central HER2 testing across multiple platforms and response to tx for MOUNTAINEER pts treated w/ TUC + Tras based on central HER2 status. Methods: MOUNTAINEER (NCT03043313) enrolled pts w/ local HER2+ mCRC using ≥1 method: IHC, ISH, and/or NGS testing; retrospective central assessment of HER2 status was performed on multiple platforms. Pts in cohorts A+B were treated w/ TUC + Tras; pts in cohort C were treated w/ TUC monotherapy. Confirmed objective response rates (cORRs) using RECIST v1.1 per BICR, DOR, and PFS were calculated for pts treated w/ TUC + Tras based on each central testing method. Results: 114 pts were enrolled in cohorts A (n = 45), B (n = 39), and C (n = 30) w/ HER2+ tumors per ≥1 local testing method. Of samples submitted for central testing for Cohorts A and B, 70 per IHC/FISH, 50 per tissue NGS, and 71 per blood NGS had evaluable results. In all cohorts, there was 81.0% (95% CI, 68.6-90.1) agreement between blood and tissue NGS, 92.6% (95% CI, 83.7-97.6) between IHC/FISH and tissue NGS, and 79.5% (95% CI, 69.2-87.6) between IHC/FISH and blood NGS. In cohorts A and B, pts w/ HER2+ tumors by central IHC/ISH had a mDOR of 16.4 months (95% CI: 10.6-25.5) and mPFS of 10.1 months (95% CI: 4.2-15.2). cORR was 41.1% to 47.7% for the 3 assays. Detailed HER2 results are presented in the Table. Conclusions: Percent agreement of HER2 status was highest w/ tissue-based platforms. Detection of HER2 amplification by ctNDA NGS is useful; however, pts w/o HER2 amplification should be confirmed w/ a tissue-based assay. HER2 status by all 3 platforms predicted tx response to TUC + Tras. cORR in IHC2+/ISH+ was numerically lower but remained clinically relevant. These data support use of the above methods to identify HER2+ mCRC patients that may benefit from TUC + Tras. Clinical trial information: NCT03043313 . [Table: see text]
Antiproliferative activity of marine-derived oligopeptides combined with androgen receptor inhibition in preclinical prostate cancer models.
Authors: Crawford Currie, Christian Bjerknes, Erland Hermansen, Bomi Framroze
Journal: Journal of Clinical Oncology (2023)

e15186 Background: Recent cancer statistics reveal a sustained increase in the incidence of prostate cancer (PC) of 3% per year. More than half of this increase is attributable to advanced disease. Advanced PC remains largely incurable, owing to inevitable progression. Escalation of therapy can restore tumor control, but significant sequelae may result. Anticancer peptides of marine origin appear intrinsically target specific and may constitute a novel approach to improve the therapeutic sensitivity of resistant cancers. Recently published in vitro work showed that a marine soluble protein hydrolysate (SPH) potentiated the anticancer effect of androgen-receptor inhibitors (ARis) in PC cells. SPH also induced transcriptional upregulation of ferritin heavy chain 1 (FTH1) in LNCaP and PC3 cell lines. Given the growing recognition that iron dysmetabolism plays a key role in PC, we applied the findings to this current study. Methods: Eight candidate FTH1-modulatory peptides (FT-001 to -008, all 7- or 8-mer peptides) were identified in the SPH peptide mix and subsequently sequenced and synthesized. Antiproliferative effects of individual FT peptides were assessed in combination with ARis (bicalutamide/BIC or enzalutamide/ENZ) in phenotypically distinct PC cell lines (LNCaP, PC3, VCaP, ENZR-VCaP) and compared to the inhibitory effect of SPH-ARi combination or ARi monotherapy. Results: FT-002 or -005 (10 μM concentration), showed significantly greater inhibition of LNCaP and PC3 cell viability when co-administered with BIC IC50 (0.4 μM &amp; 10 μM respectively), than SPH (160 μM) with BIC or BIC monotherapy (p &lt; 0.001). Similarly, either peptide combined with ENZ IC50 (1.4 μM) exhibited significant antiproliferative effects on androgen-sensitive VCaP cells when compared to SPH (160 μM) &amp; ENZ co-treatment (p &lt; 0.01) and ENZ monotreatment (p &lt; 0.001). Both peptides (10 μM) produced a similar pattern of results in ENZ-resistant VCaP cells when treated with ENZ at its corresponding IC50 (47 μM) (p &lt; 0.001). Differential gene expression profiling of all tested cells showed a consistent and significant upregulation of FTH1 and concomitant downregulation of transferrin receptor (TFRC) gene expression of greater than 2-fold for FT/ARi therapy. Conclusions: FT-002 and -005 synergistically combine with ARis to significantly attenuate PC tumor growth in vitro. Gene expression profiling implicates peptide-mediated FTH1 and TFRC modulation in the mode of action to interfere with tumor cell iron metabolism. Novel research perspectives implicate ferritin and FTH1 expression levels in prostate carcinogenesis and tumor progression. Further research in xenograft models is warranted, in order to validate the current findings and further investigate the cellular pathways responsible for the observed anticancer activity seen with FT-002 and FT-005.
Population pharmacokinetic and exposure-response safety analyses of mecbotamab vedotin (BA3011) in patients with advanced solid tumors.
Authors: Guoxiang George Shen, Emily Briggs, Ryan Crass, Sravan Karumanchi, William J. Boyle, Michael G. Baker, Philippe Martin
Journal: Journal of Clinical Oncology (2023)

e15010 Background: Mecbotamab vedotin (BA3011) is antibody-drug conjugate (ADC) consisting of a conditionally active biologic (CAB) anti-AXL humanized (IgG1) monoclonal antibody conjugated to monomethyl auristatin E (MMAE) using a cleavable linker. BA3011 is being developed for the treatment patients with advanced solid tumors including sarcoma with AXL expression. Methods: As of data cutoff date 19 April 2022, BA3011 was administered by intravenous infusion to 67 patients, with doses ranged from 0.3 to 3 mg/kg once every three weeks (Q3W), 1.2 to 1.8 mg/kg once every two weeks (Q2W) and 1.8 mg/kg twice every three weeks (2Q3W). Population pharmacokinetics (popPK) analysis was performed using sequential modeling approach, where a PK model was first developed for BA3011 ADC alone, and then an integrated model was developed for BA3011 ADC and MMAE. The popPK base model for BA3011 ADC and MMAE was used to generate empirical Bayes estimates of PK parameters for patients in Study BA3011-001 and used for the exposure-response (E-R) safety analysis. E-R time-to-event models were developed to characterize the relationship between BA3011 ADC or MMAE exposure and the time to first incidence of adverse events (AEs). Results: A popPK model with two-compartment disposition and parallel linear and nonlinear elimination of BA3011 ADC, formation of MMAE from ADC, and two-compartment disposition and linear elimination of MMAE, adequately described the PK profiles of BA3011 ADC and MMAE in patients based on model evaluation using prediction-corrected visual predictive checks. Key PK parameter estimates are summarized in the table below. In the E-R safety analysis, statistically significant correlations were demonstrated between BA3011 ADC exposure and all safety endpoints explored (TEAE Grade ≥3, neutropenia Grade ≥3, increase in AST or ALT Grade ≥1, anemia Grade ≥2, and peripheral neuropathy Grade ≥1). Correlations were statistically significant between MMAE exposure and TEAE Grade ≥3, neutropenia Grade ≥3, increase in AST or ALT Grade ≥1, but not anemia Grade ≥2 or peripheral neuropathy Grade ≥1. Time-varying Cmax was selected as the most appropriate exposure metric for each model developed, calculated over the past 24 hours, 1 week, or 3 weeks, depending on the model. Conclusions: The popPK relationship between ADC and MMAE were adequately characterized using a sequential modeling approach. BA3011 ADC exposure was correlated with all safety endpoints evaluated whereas MMAE exposure did not demonstrate correlations with anemia or peripheral neuropathy. These models are essential to generate predictions of exposure and safety for dosing regimens to be evaluated in a planned Phase 2 clinical trial. Clinical trial information: NCT03425279 . [Table: see text]
Assessment of price variation in colorectal cancer screening procedures at US hospitals.
Authors: Ishan Paranjpe, Pranav Sharma, Chen Wei, Vikram Puram, Samir Kamat, Ali Raza Khaki
Journal: Journal of Clinical Oncology (2023)

6652 Background: Following the 2021 Hospital Price Transparency Final Rule, US hospitals were mandated to publish their insurer-negotiated prices. We identified factors contributing to price variability of colorectal cancer (CRC) screening procedures across the US. Methods: We compared prices of colonoscopy, flexible sigmoidoscopy, CT colonography, fecal occult blood test, fecal immunochemical test, and Cologuard across U.S. hospitals using the Turquoise dataset (N = 6,378). Psychiatric, rehabilitation, and pediatric hospitals were excluded. Prices in the top and bottom 1% were also excluded to minimize the effect of outliers. Prices were adjusted by the Medicare Geographic Price Index to account for regional variability. We then compared prices across several subgroups, including National Cancer Institute (NCI) designated hospitals, teaching hospitals, and investor owned hospitals. Significance was assessed using the Kruskal-Wallis test. To quantify price variability across insurance plans within a hospital, we defined the within-center-ratio as the 90 th percentile rate at a hospital divided by the 10 th percentile rate. To quantify variability across hospitals, the across-center-ratio was defined as the 90 th percentile median rate across all hospitals divided by the 10 th percentile median rate. Results: 1,460 hospitals reported commercial prices for colonoscopy with a median commercial price of $1,867 (IQR: $1,208 - $2,689). For colonoscopy, the within center ratio was 2.5 (IQR: 1.5 – 3.8) and the across-center ratio was 6.2. Prices for other procedures are provided in the table. Compared to non-investor owned hospitals, prices of colonoscopy ($2,082 vs $1,787, P &lt;0.001) and flexible sigmoidoscopy ($2,022 vs $1,289, P &lt;0.001) were significantly higher at investor owned hospitals. Furthermore, across investor classes, hospitals with &gt;5% ownership from private equity firms had the highest median price for both colonoscopy ($2,898), and flexible sigmoidoscopy ($2,697). We did not find significant differences in price by NCI designation, academic teaching center affiliation, overall hospital mortality, overall hospital readmission rate, or urban/rural location. Conclusions: CRC screening procedure prices vary significantly both within and across hospitals. Private equity and other investor owned hospitals had significantly higher prices compared to non-investor owned hospitals. [Table: see text]
Use of circulating tumor DNA analysis to predict recurrence and need for adjuvant chemotherapy in stage I-IV colorectal cancer.
Authors: Li-Ren Li, Wenhua Fan, Zhiyuan Xia, Rongrong Chen, Dagui Lin, Fang Li, Yang Zheng, Jiongyong Luo, Yuanyuan Xiong, Pengli Yu, Wei Gao, Yuhua Gong, Sen Zhang, Feiran Zhang
Journal: Journal of Clinical Oncology (2023)

e15537 Background: Circulating tumor DNA (ctDNA) has emerged as a biomarker that can define the risk of recurrence after curative-intent surgery for patients with colorectal cancer (CRC). However, beyond the predictive power of postoperative ctDNA detection, the efficacy and potential limitations of ctDNA detection urgently need to be fully elucidated in a large cohort of CRC. Methods: We enrolled 309 patients with stages Ⅰ to Ⅳ CRC who underwent definitive surgery. Tumor tissues from those patients were sequenced by a custom-designed next-generation sequencing (NGS) panel to identify somatic mutations, and plasma was analyzed using ctDNA-based molecular residual disease (MRD) assay which integrated tumor genotype–informed and tumor genotype–naïve ctDNA analysis. Results: ctDNA was detected after surgery in 5.4%, 13.8%, 15% and 30% of patients with stage Ⅰ, Ⅱ, Ⅲ and Ⅳ disease, respectively, and in 17.5% of all longitudinal samples. Detection of MRD after surgery and in serial plasma samples during follow-up were associated with shorter disease-free survival (DFS) (hazard ratio [HR], 13.17; P &lt; 0.0001 and HR, 14.44; P &lt; 0.0001, respectively) independent of tumor site, stage, and MSI status. Within the population, only 13 patients (6.6%) with longitudinal undetectable MRD recurred, resulting in a negative predictive value of 93.4%. Correspondingly, the positive predictive value of longitudinal detectable MRD was 79.6%, with a median lead time of 10.1 months. Further subgroup analyses revealed that adjuvant therapy did not confer a superior survival for patients with undetectable or detectable MRD. Moreover, lung-only and peritoneal metastases were less detectable by MRD. Conclusions: Postoperative ctDNA status is a strong predictor of recurrence independent of stage and MSI status. Longitudinal undetectable MRD could be used to define the potentially cured population in CRC patients undergoing curative-intent surgery.